The promoters for human DNA-PKcs (PRKDC) and MCM4: divergently transcribed genes located at chromosome 8 band q11.
A 30-kb genomic segment containing the promoter and first 9 exons of PRKDC, the gene encoding the catalytic subunit (DNA-PKcs) of the human DNA-activated protein kinase, DNA-PK, was isolated and partially sequenced. Sequence comparison with the NCBI nonredundant database revealed the locations of the first 13 exons of the upstream gene, MCM4. MCM4 is an essential component of a protein complex that prevents DNA from being replicated more than once per cell cycle. The MCM4 and DNA-PKcs promoters are in CpG islands separated by approximately 700 bp, and transcription from each initiates at multiple, closely spaced sites. Both promoters lack TATA boxes, and the MCM4 promoter also lacks an initiator (Inr) element but has an inverted CCAAT box. The DNA-PKcs promoter has an Inr-like sequence as well as a downstream MED-1 element. The two promoters appear to function independently, as sequences required for core promoter activity do not overlap, and sequences extending into the 5' region of each gene had little or no effect on transcription of the other gene, as shown in transient transfection assays. The arrangement of the PRKDC/MCM4 gene pair is similar to that of the ATM/E14(NPAT) gene pair. ATM, the product of the gene mutated in ataxia telangiectasia, and DNA-PKcs function in pathways that detect or repair DNA damage and are members of a family of large, serine/threonine kinases that are closely related to phosphatidylinositol 3 kinases.
Connelly
M A
MA
Biology Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Zhang
H
H
Kieleczawa
J
J
Anderson
C W
CW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002898:Chromosomes, Human, Pair 8; D004265:DNA Helicases; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D006801:Humans; D051379:Mice; D064148:Minichromosome Maintenance Complex Component 4; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C497264:Prkdc protein, mouse; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C099243:MCM4 protein, human; C516793:Mcm4 protein, mouse; D064148:Minichromosome Maintenance Complex Component 4